Functional characterization of specialized metabolites from gut microbiomes

Project Information

SMs-Gut

Grant agreement ID: 894369

DOI

10.3030/894369

Project closed

EC signature date 28 April 2020

Start date 1 November 2020

End date 31 October 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 174 806,40

EU contribution

€ 174 806,40

Coordinated by

TECHNISCHE UNIVERSITAET DRESDEN
Germany

Periodic Reporting for period 1 - SMs-Gut (Functional characterization of specialized metabolites from gut microbiomes)

Reporting period: 2020-11-01 to 2022-10-31

Summary of the context and overall objectives of the project

Gut-related diseases, such as CRC and IBC, pose significant health threats to mankind. Yet the mechanisms for their development and progression are still not well understood. In particular, the potential role of the gut microbiota and their specialized metabolism in this context is fully unclear. Understanding the impact of the interaction of gut microbiota and host in the context of disease is crucial to develop better preventive measures and treatment options and thus has the potential to help solve important medical questions. Within this project, novel methods for the targeted discovery, production, and functional study of specialized gut metabolism have been developed. These tools are important to enable future systematic studies on gut health and disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The performed work included the bioinformatic mapping of the biosynthetic potential of selected members of human and mouse gut microbiota, the development of new cloning techniques for the interception of biosynthetic pathways, the heterologous expression of such pathways in E. coli, and the isolation of the respective small molecule products, in addition to the functional characterization of the latter in the context of human diseases development. This led, i.a. to the discovery of yet unknown selective cytotoxins produced by a gut bacterium that might play a role in CRC development of progression. The results of this work are currently being processed for publication.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project provides a new approach for the direct cloning of large (>25 kb) biosynthetic pathways for recombinant production of small molecules. In addition, yet unknown deleterious effects of small molecules produced by gut microbiota have been identified. These findings will help develop streamlined platforms for small molecular discovery from the gut and beyond and have the potential to help develop novel approaches for the diagnosis of CRC-promoting factors and for the treatment of gut diseases.

Schematic workflow of the research project